The overall goal of this Program Project is to improve the outcome of allogeneic transplantation in the treatment of hematologic malignancies. General topics to be addressed include expansion of the donor pool, eradication of malignancy, and development of methods to prevent transplant-related complications. Nine projects are proposed: Allogeneic peripheral Blood Stem Cell Transplantation in Matched Siblings Alternative Donors Prevention and Treatment of Graft-versus-host Disease Tolerance Induction by Therapeutic Monoclonal Antibodies Pathophysiology and Prevention of Multi-organ Failure Detection and Treatment of Minimal Residual Disease Prevention and Treatment of Infection Specific Adoptive Immunotherapy of Viral Disease Treatment of Malignancy with Gene-modified T cells and T cell Clones Our ability to carry out the proposed studies in this Program Project is enhanced by: 1) preclincial research programs involving animal models which allow rapid and logical translation of preclinical concepts to clinical trails; 2) the accrual of 300-350 allogeneic transplant patients onto research studies each year; 3) core support in biostatistics, pathology, microbiology, pharmacology, gastroenterology, stem cell processing, long-term follow-up and administration; and 4) our unique structure as a large group of investigators all focused on the general topic of hematopoietic transplantation. Success in the achievement of our goal will likely have relevance for the use of other intensive or immune-based therapies to treat hematologic malignancies, for the wider application of these approaches intensive or immune- based therapies to treat hematologic malignancies, for the wider application of these approaches to the treatment of other malignant and non-malignant diseases and for the care of immunocompromised patients.